79583-98-5Relevant articles and documents
Conjugation of an oligonucleotide to Tat, a cell-penetrating peptide, via click chemistry
Brown, Sarah D.,Graham, Duncan
, p. 5032 - 5034 (2010)
Uptake of diagnostic and therapeutic oligonucleotides that specifically target disease can be enhanced by attachment of a cell-penetrating peptide. Here, we describe the covalent attachment of an oligonucleotide to Tat, a biologically important cell-penetrating peptide, via click chemistry.
Preliminary evaluation of 18F-labeled LLP2A-trifluoroborate conjugates as VLA-4 (α4β1 integrin) specific radiotracers for PET imaging of melanoma
Roxin, áron,Zhang, Chengcheng,Huh, Sungjoon,Lepage, Mathieu L.,Zhang, Zhengxing,Lin, Kuo-Shyan,Bénard, Fran?ois,Perrin, David M.
, p. 11 - 20 (2018)
Introduction: The transmembrane α4β1 integrin receptor, or very-late antigen 4 (VLA-4), is associated with tumor metastasis and angiogenesis, the development of chemotherapeutic drug resistance, and is overexpressed in multiple myelomas, osteosarcomas, lymphomas, leukemias, and melanomas. The peptidomimetic, LLP2A, is a high-affinity ligand with specificity for the extracellular portion of VLA-4 and several conjugates have been evaluated in vivo by NIR-fluorescence, 111In-SPECT and 68Ga- and 64Cu-PET imaging, but to date, not with 18F-PET. Methods: Using two highly stable organotrifluoroborate prosthetic groups: ammoniumdimethyl-trifluoroborate (AMBF3) and a new N-pyridinyl-para-trifluoroborate (N-Pyr-p-BF3), both capable of facile aqueous 18F-labeling by isotope exchange (IEX), we present the first PET imaging evaluations of two [18F]R-BF3 ?–PEG2-LLP2A tracers using VLA-4 overexpressing B16-F10 murine melanoma tumor mouse models. Results: Here, we demonstrate successful one-step 18F-labeling of both conjugates with wet NCA [18F]F? in radiochemical yields of up to 11.6% within 75 min at molar activities of 40–100 GBq/μmol. Average tumor uptake values based on ex vivo biodistribution values were 4.4%ID/g (11) and 2.8%ID/g (12) using 18F-labeled LLP2A-conjugates with the two prosthetic groups: N-Pyr-p-BF3 (5) and alkyl-N,N-dimethylammonio-BF3 (AMBF3) (7), respectively, and was found to be target-specific as evidenced by in vivo blocking controls. Dynamic PET scanning and biodistribution studies revealed slow clearance of the [18F]R-BF3 ?–PEG2-LLP2A tracers from the tumors, and also substantial uptake in the intestines, gall bladder, liver and bladder. Observed bone uptake was blockable, consistent with known VLA-4 expression in hematopoietic stem cells found in bone marrow. Conclusions: These studies show that these [18F]R-BF3 ?–PEG2-LLP2A conjugates (11 and 12) are promising VLA-4 targeting radiotracers, yet, further optimization will be required to reduce uptake in the gastro-intestinal tract.
Hypervalent Iodine Based Reversible Covalent Bond in Rotaxane Synthesis
Kandrnálová, Markéta,Kokan, Zoran,Havel, Václav,Ne?as, Marek,?indelá?, Vladimír
, p. 18182 - 18185 (2019)
Reversible covalent bonds play a significant role in achieving the high-yielding synthesis of mechanically interlocked molecules. Still, only a handful of such bonds have been successfully employed in synthetic procedures. Herein, we introduce a novel app
Modulation of the Passive Permeability of Semipeptidic Macrocycles: N- And C-Methylations Fine-Tune Conformation and Properties
Boudreault, Pierre-Luc,Comeau, Christian,Derbali, Rabeb Mouna,Grandbois, Michel,Poulet, Sylvain,Ries, Benjamin,Riniker, Sereina,Sarret, Philippe,Stadelmann, Thomas,Tremblay, Jacob,C?té, Jér?me,Fr?hlich, Ulrike,Leclair, Grégoire,Marsault, éric
, p. 5365 - 5383 (2021/05/04)
Incorporating small modifications to peptidic macrocycles can have a major influence on their properties. For instance, N-methylation has been shown to impact permeability. A better understanding of the relationship between permeability and structure is of key importance as peptidic drugs are often associated with unfavorable pharmacokinetic profiles. Starting from a semipeptidic macrocycle backbone composed of a tripeptide tethered head-to-tail with an alkyl linker, we investigated two small changes: peptide-to-peptoid substitution and various methyl placements on the nonpeptidic linker. Implementing these changes in parallel, we created a collection of 36 compounds. Their permeability was then assessed in parallel artificial membrane permeability assay (PAMPA) and Caco-2 assays. Our results show a systematic improvement in permeability associated with one peptoid position in the cycle, while the influence of methyl substitution varies on a case-by-case basis. Using a combination of molecular dynamics simulations and NMR measurements, we offer hypotheses to explain such behavior.
Discovery of triazolyl thalidomide derivatives as anti-fibrosis agents
Tang, Kai-Wei,Hsu, Wen-Li,Chen, Cheng-Ru,Tsai, Ming-Hsien,Yen, Chia-Jung,Tseng, Chih-Hua
, p. 3589 - 3599 (2021/03/03)
Fibrosis with excessive accumulation of extracellular matrix (ECM) often causes progressive organ dysfunction and results in many inflammatory and metabolic diseases, including systemic sclerosis, pulmonary fibrosis, advanced liver disease and advanced kidney disease. The store-operated calcium entry (SOCE) pathway and the related signaling pathway were both found to be the important routes for fibrogenesis. Our aim in this study was to discover novel compounds to inhibit fibrogenesis. A number of triazolyl thalidomide derivatives were synthesized and evaluated for their anti-fibrosis activities. Compounds 7b-e, 8c-d, 10a-b and 10e inhibited intracellular Ca2+ activation and showed no cytotoxicity. Among them, 6-{4-[(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl]-1H-1,2,3-triazol-1-yl}hexanoic acid (10e) with the most potent inhibitory effect was chosen for further examination. The results revealed that compound 10e, a SOCE inhibitor, reversed the migratory ability of TGF-β1-induced myofibroblasts, dedifferentiated myofibroblasts to fibroblasts due to cytoskeleton remodeling, and restrained myofibroblast activation by targeting Orai1 and TGF-β1/SMAD2/3 signaling pathways. The in silico study indicated that compound 10e, with the appropriate lipophilic carbon chain and carboxylic acid, showed a good drug-likeness model score. Conclusively, the SOCE inhibitor, compound 10e, is used as a promising lead compound for the development of a new treatment for fibrosis. This journal is
ENVIRONMENTALLY-FRIENDLY HYDROAZIDATION OF OLEFINS
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Page/Page column 62; 79-80, (2020/01/24)
The present invention provides processes for the synthesis of organic azides, intermediates for the production thereof, and compositions related thereto.
